Engineering The Next Generation of Cancer Therapeutic Enzymes and Antibodies
George Georgiou, University of Texas, Austin
Friday, May 21, 2010
This seminar is part of the Jones Seminars on Science, Technology, and Society series
Our lab is broadly interested in the development of platform technologies for the discovery and pharmacological development of therapeutic proteins, especially for cancer. In recent years there has been intense interest on the metabolic abnormalities displayed by cancer cells and how these effects may be exploited for therapeutic purposes. The use of enzymes to systemically deplete metabolites required for the growth of tumor cells but not of normal tissues, has been pursued for many years. However with the exception of childhood leukemia (ALL) where administration of the bacterial enzyme Asparaginase has been shown to have significant therapeutic benefit, no other enzyme drugs for cancer treatment have been developed. This is because bacterial enzymes elicit strong adverse responses due to immunogenicity whereas human enzymes that display either the proper catalytic activity or pharmacological properties for reactions relevant to cancer therapy are not available. We have been using protein engineering strategies to create human enzymes that display new catalytic properties of therapeutic relevance and also the proper stability and in vivo persistence appropriate for therapeutic applications. We have developed a family of such therapeutics for various malignancies. One such example, an engineered human arginase I for the treatment of liver cancer and metastatic melanoma, is now in advanced preclinical development. In parallel we have been developing a number of technologies for the isolation of IgG antibodies to cancer antigens and for the enhancement of Fc-mediated effector functions. A summary of this work will also be presented.
About the Speaker
George Georgiou is the Cockrell Endowed Professor at the University of Texas, Austin where he has joint appointments in the Departments of Chemical Engineering, the Section of Molecular Genetics and Microbiology and Biomedical Engineering. He is also a member of the Institute for Cell and Molecular Biology at the University of Texas, Austin. He received his B.Sc. degree from the University of Manchester, U.K. and his Ph.D. from Cornell in 1987. He is a member of the U.S. National Academy of Engineering and a Fellow of the American Society for Microbiology, the American Association for the Advancement of Sciences, and the American Institute of Medical and Biological Engineers. He has received numerous awards including the AIChE Professional Progress Award for outstanding contributions to Chemical Engineering by an individual under 45 (2003) and was named as "One of the Top 100 Eminent Chemical Engineers of the Modern Era" by AIChE (2008). His research is focused on the discovery and pharmacological optimization of protein therapeutics and also on the mechanisms of redox homeostasis and protein secretion in bacteria. Dr. Georgiou and his collaborators have developed one anti-infective antibody drug (Anthem™, currently in late stage clinical development), an array of therapeutic enzymes in preclinical development, and finally, antibodies for cancer chemotherapy. Dr. Georgiou has published >170 research articles and is co-inventor of 38 US patent applications of which 26 have been licensed to pharmaceutical and biotechnology companies.